Secretion of the granule contents of neutrophils contributes to acute inflammation and to the chronic tissue destruction characteristic of many human diseases. The ultimate regulators of granule membrane- plasma membrane fusion have not yet been characterized. The Investigator developed a highly efficient and reproducible method that introduces large pores into the plasma membrane of neutrophils, allowing free exchange of cytoplasmic proteins with the extracellular medium. The permeabilized neutrophils efficiently secrete lactoferrin in response to 1 Mm free calcium. Using this system, the Investigator will examine the role of annexin I, phospholipid metabolites and GTPases in regulating secretion.